Construction and phenotypic analysis of an animal model of dilated cardiomyopathy induced by NEXN gene mutation

AIM To construct a genetically engineered mouse model of dilated cardiomyopathy.

METHODS The NEXN gene was knocked out using CRISPR/Cas9 technology in C57BL/6J mice. The knockout mice were identified through PCR and Sanger sequencing. Macroscopic anatomy was used to observe cardiac morphology, while HE and Masson staining were employed to analyze pathological changes in the tissue. Echocardiography was conducted to assess cardiac function in the knockout mice.

RESULTS Under the guidance of sgRNA, an 11bp sequence in exon 9 of the NEXN gene was knocked out, resulting in a frameshift mutation that led to premature termination of translation, producing a truncated nexilin protein (P<0.05). The NEXN gene mutated mice exhibited enlarged cardiac volume, increased heart mass to body weight ratio (P<0.05), significant pathological changes in tissues, marked ventricular dilation and severe decline in cardiac function.

CONCLUSION A genetically engineered mouse model of dilated cardiomyopathy is successfully constructed by mutating the NEXN gene and the phenotypic characteristics of the model mice are consistent with those of dilated cardiomyopathy.